Multicentric Analytical and Inter-observer Comparability of Four Clinically Developed Programmed Death-ligand 1 Immunohistochemistry Assays in Advanced Clear-cell Renal Cell Carcinoma

Abstract

Background: Previous studies have suggested increased clinical benefit with inhibition of programmed death-ligand 1 (PD-L1)/programmed death-1 in patients with PD-L1-positive locally advanced/metastatic renal cell carcinoma (RCC). We examined the analytical and inter-observer comparability of PD-L1-positivity across 4 clinically developed immunohistochemistry assays in clear-cell RCC (CCRCC).

Materials and methods: Randomly selected archived, formalin-fixed, paraffin-embedded nephrectomy specimens from 201 patients with locally advanced CCRCC were screened using VENTANA SP142. From these, 30 cases were selected based on their tumor-infiltrating immune cell (IC) PD-L1 status (PD-L1-IC-positivity of < 1%, 1%-5%, or > 5%; 10 cases each). These cases were stained for PD-L1 using VENTANA SP142 and SP263, and DAKO 22C3 and 28-8, and scored for PD-L1 expression on IC and tumor cells (TC) by trained readers at 5 sites.

Results: Adjusted mean percentages of PD-L1-IC-positivity and PD-L1-TC-positivity varied from 4.0% to 4.9% and from 1.3% to 10.7%, respectively, between assays. Inter-assay differences in PD-L1-IC-positivity were small and non-significant (P = .1938 to .9963); for PD-L1-TC-positivity, significant differences were observed between VENTANA SP142 and the other assays (P ≤ .0001) and between VENTANA SP263 and DAKO 28-8 (P = .0248). Intra-class correlation values showed moderate-to-high inter-reader agreement for each assay for PD-L1-IC-positivity and for 3 assays for PD-L1-TC-positivity.

Conclusions: In this first multicenter analytical comparison study of PD-L1 assays in CCRCC, PD-L1-positivity could be assessed reproducibly using all 4 assays for IC and for 3 of the 4 assays for TC.

Keywords: CCRC; Inter-observer variability; PD-L1; PD-L1 assay; Technical comparability; Uropathology.